Team ATLAS, the international Cancer Grand Challenges team that includes researchers from the Ludwig Institute for Cancer Research, has marked two early milestones: the publication of a position paper setting out the project’s scientific framework, and the completion of its kick-off meeting, held in Paris.
The team, which includes Professor Xin Lu (Director of the Oxford Branch) and Professor Chi Van Dang (CEO and Scientific Director of the Ludwig Institute for Cancer Research), has been awarded up to $25 million over approximately five years by Cancer Grand Challenges to tackle the cancer avoidance challenge: investigating why cancer arises, progresses, or proves fatal in some people, while others with similar risks remain cancer-free.
In the paper, published in Cell, team ATLAS proposes that antibody repertoires – including autoantibodies that target immune pathways – may help shape cancer immunosurveillance. These naturally occurring antibodies may influence whether the immune system can eliminate emerging cancer cells, allow them to escape, or affect how patients respond to treatment. They may also provide a record of a person’s immune history, including previous exposure to infections, self-antigens or cancer-related antigens.
This record could be particularly important for understanding why patients respond differently to some treatments. For example, immune checkpoint inhibitors have transformed treatment for some cancers by releasing the brakes on anti-tumour immune responses, but only a subset of patients benefit from these therapies. The ATLAS team thinks that pre-existing antibody repertoires may be one factor influencing whether patients respond to treatment, develop resistance, or experience immune-related side effects.
To investigate this, the team will compare antibodies found in cancer-free individuals, people at increased risk of cancer, and patients with different cancers. Using technologies that can screen antibody responses against thousands of self, cancer-related and non-self antigens, they will build a comprehensive cancer antibody atlas. By comparing antibody profiles across these groups, the researchers aim to identify signatures linked to cancer avoidance, susceptibility, progression and treatment response.
This approach could have several future applications. Antibody signatures could be used as biomarkers to help identify people at higher risk of developing cancer, enable earlier detection, or improve how patients are matched to existing treatments such as checkpoint inhibitors. Functional antibodies could also reveal new biological pathways involved in cancer avoidance or progression, helping to identify new opportunities for cancer prevention and therapy.
The project is now well underway following the recent kick-off meeting, which brought together Cancer Grand Challenges coordinators, funders, and the international ATLAS team. Participants included clinicians, patient advocates and scientists with expertise spanning ageing, early detection, immunology, paediatrics, prevention and more. The meeting focused on the project’s scientific background and strategy, including how the team will meet its study goals and analyse data to determine the role of autoantibodies in cancer avoidance.
Professor Xin Lu said:
“This project gives us an important opportunity to identify antibodies, including cancer-associated autoantibodies, that may be involved in cancer avoidance and survival. These antibody signatures could help us understand why some people remain cancer-free despite being at increased risk, and why some patients respond to treatment better than others.”
By mapping the antibody landscapes associated with cancer avoidance and outcome, team ATLAS hopes to identify signatures that could inform approaches to risk prediction, earlier detection and the selection or development of treatments.
To find out more about team ATLAS, visit their website, or read the full paper here.
About Cancer Grand Challenges
Co-founded in 2020 by two of the largest funders of cancer research in the world: Cancer Research UK and the National Cancer Institute, Cancer Grand Challenges supports a global community of diverse, world-class research teams to come together, think differently and take on some of cancer’s toughest challenges. These are the obstacles that continue to impede progress and no one scientist, institution or country will be able to solve them alone. With awards of up to $25 million, Cancer Grand Challenges teams are empowered to rise above the traditional boundaries of geography and discipline to make progress against cancer we urgently need.
Cancer Grand Challenges brings together 1,800 researchers and 21 teams from across the world to take on 18 challenges.